Potential immunogenicity of adult T cell leukemia cells in vivo

Kiyoshi Kurihara, Nanae Harashima, Shino Hanabuchi, Masato Masuda, Atae Utsunomiya, Ryuji Tanosaki, Masao Tomonaga, Takashi Ohashi, Atsuhiko Hasegawa, Takao Masuda, Jun Okamura, Yuetsu Tanaka, Mari Kannagi

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Experimental vaccines targeting human T cell leukemia virus type-I (HTLV-I) Tax have been demonstrated in a rat model of HTLV-I-induced lymphomas. However, the scarcity of HTLV-I-expression and the presence of defective HTLV-I-proviruses in adult T cell leukemia (ATL) cells have raised controversy about the therapeutic potential of HTLV-I-targeted immunotherapy in humans. We investigated the expression of HTLV-I antigens in fresh ATL cells by using both in vitro and in vivo assays. In flow cytometric analysis, we found that 3 of 5 acute-type and six of fifteen chronic-type ATL patients tested showed significant induction of HTLV-I Tax and Gag in their ATL cells in a 1-day culture. Concomitantly with HTLV-I-expression, these ATL cells expressed co-stimulatory molecules such as CD80, CD86 and OX40, and showed elevated levels of antigenicity against allogeneic T cells and HTLV-I Tax-specific cytotoxic T-lymphocytes (CTL). Representative CTL epitopes restricted by HLA-A2 or A24 were conserved in 4 of 5 acute-type ATL patients tested. Furthermore, spleen T cells from rats, which had been subcutaneously inoculated with formalin-fixed uncultured ATL cells, exhibited a strong interferon gamma-producing helper T cell responses specific for HTLV-I Tax-expressing cells. Our study indicated that ATL cells from about half the patients tested readily express HTLV-I antigens including Tax in vitro, and that ATL cells express sufficient amounts of Tax or Tax-induced antigens to evoke specific T cell responses in vivo.

Original languageEnglish
Pages (from-to)257-267
Number of pages11
JournalInternational Journal of Cancer
Volume114
Issue number2
DOIs
Publication statusPublished - 2005 Mar 20
Externally publishedYes

Keywords

  • Cancer vaccine
  • Co-stimulatory molecules
  • Human T cell leukemia virus type-I (HTLV-I)
  • T cell immune response
  • Viral expression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Kurihara, K., Harashima, N., Hanabuchi, S., Masuda, M., Utsunomiya, A., Tanosaki, R., Tomonaga, M., Ohashi, T., Hasegawa, A., Masuda, T., Okamura, J., Tanaka, Y., & Kannagi, M. (2005). Potential immunogenicity of adult T cell leukemia cells in vivo. International Journal of Cancer, 114(2), 257-267. https://doi.org/10.1002/ijc.20737